Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human vascular smooth muscle cells at multiple signaling levels

1928 Platelet-derived growth factor (PDGF) has been known to induce vascular endothelial growth factor (VEGF) expression in human vascular smooth muscle cells (hVSMCs). Previously, we reported that Erk-1/2 and AP-1 pathways are crucial in the PDGF-induced VEGF expression in hVSMCs (Int. J. Onc. 2005). In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG) on the PDGF-induced VEGF expression in hVSMCs and the underlying molecular mechanisms. EGCG were found to inhibit dose-dependently the VEGF expression and activation of PDGF receptor, Erk-1/2 and AP-1 induced by PDGF. Moreover, cell free studies demonstrated that EGCG could directly inhibit the Erk-1/2 activities and AP-1-DNA binding. Conditioned media from the hVSMCs treated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells (HUVEC) but the media from the EGCG-pretreated hVSMCs lost the stimulatory activity for HUVEC proliferation. These results suggest that EGCG may exert the anti-angiogenic effect by inhibiting the PDGF-induced VEGF expression at multiple signaling levels.